Surface dependent activation of Hageman factor was shown to require prekallikrein and high molecular weight (HMW) kininogen. Prekallikrein and HMW kininogen circulate in plasma as a complex and HMW kininogen functions as a cofactor in the reciprocal activation of Hageman factor and prekallikrein. Activated Hageman factor cleaves prekallikrein within a disulfide bridge to yield a two-chain disulfide linked kallikrein; the active site of kallikrein is in the light chain. Kallikrein directly converts plasminogen to plasmin and digests HMW-kininogen to yield bradykinin. The light chain of HMW kininogen is responsible for all of its coagulant activity and the heavy chain is the portion in common with low mol. wt. kininogen. Factor XI also circulates bound to HMW kininogen and factor XIA-HMW kininogen functions as an alternative complex enzyme that activates Hageman factor and factor XIA is an alternative activator of plasminogen. This accounts for the auto correction of prekallikrein deficient plasma. Assessment of induced blisters over urticarial lesions has identified histamine as one of the vasoactive mediators of cold urticaria, solar urticaria, local heat urticaria, and immediate pressure urticaria. Elevated blister fluid histamines in chronic idiopathic urticaria was also identified and is the first abnormality of mediator release defined in that disorder. BIBLIOGRAPHIC REFERENCES: Meier, H.L., Pierce, J.V., Colman, R.W., and Kaplan, A.P.: Activation and function of human Hageman factor: The role of high molecular weight kininogen and prekallikrein. J. Clin. Invest. 60: 18-31, 1977. Clark, R.A.F., Sandler, J.A., Gallin, J.I., and Kaplan, A.P.: Histamine modulation of eosinophil migration. J. Immunol. 118: 137-147, 1977.